Article

Detection of unidentified chromosome abnormalities in human neuroblastoma by spectral karyotyping (SKY)

Department of Pediatric Hemato-Oncology and Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
Genes Chromosomes and Cancer (Impact Factor: 3.84). 07/2001; 31(3):201-8. DOI: 10.1002/gcc.1136
Source: PubMed

ABSTRACT Spectral karyotyping (SKY) is a novel technique based on the simultaneous hybridization of 24 fluorescently labeled chromosome painting probes. It provides a valuable addition to the investigation of many tumors that can be difficult to define by conventional banding techniques. One such tumor is neuroblastoma, which is often characterized by poor chromosome morphology and complex karyotypes. Ten primary neuroblastoma tumor samples initially analyzed by G-banding were analyzed by SKY. In 8/10 tumors, we were able to obtain additional cytogenetic information. This included the identification of complex rearrangements and material of previously unknown origin. Structurally rearranged chromosomes can be identified even in highly condensed metaphase chromosomes. Following the SKY results, the G-banding findings were reevaluated, and the combination of the two techniques resulted in a more accurate karyotype. This combination allows identification not only of material gained and lost, but also of breakpoints and chromosomal associations. The use of SKY is therefore a powerful tool in the genetic characterization of neuroblastoma and can contribute to a better understanding of the molecular events associated with this tumor.

0 Followers
 · 
86 Views
  • Source
    • "All cases were studied using G-banding and SKY according to standard procedures [12] [14]. Except for case 20, all other cases were previously published: cases 1–10 in [12], cases 11–17 in [13] and cases 18–19 in [15]. Case 20 is the cell line STA-BT-1 that was generated from glioblastoma multiform cells of a patient who was born in November 1972 and suffered from neurofibromatosis type 1, non-Hodgkin lymphoma, (chemo-and radiation therapy of the brain), and glioblastoma grade IV, (radio therapy 40 Gy), and who died in April 1990. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Malignant solid tumors are commonly characterized by a large number of complex structural and numerical chromosomal alterations, which often reflect the level of genomic instability and can be associated with disease progression. The aim of this study was to evaluate whether chromosomes that harbor primary aberrations have a higher susceptibility to accumulate further alterations. We used spectral karyotyping (SKY), to compare the individual chromosomal instability of two chromosome types: chromosomes that have a primary aberration and chromosomes without an aberration, in 13 primary childhood neural tumors and seven cell lines. We found that chromosomes that contain a primary aberration are significantly (p-value<0.001) more likely to gain further structural rearrangements or to undergo numerical changes (22.6%, 36 of 159 chromosomes) than chromosomes with no initial aberration (4.9%, 54 of 1099 chromosomes). These results are highly suggestive that aberrant chromosomes in solid tumors have a higher susceptibility to accumulate further rearrangements than "normal" chromosomes.
    Cancer Letters 05/2007; 250(1):47-52. DOI:10.1016/j.canlet.2006.09.015 · 5.62 Impact Factor
  • Source
    • "This diverse biological behavior makes NB a paradigm for the investigation of genomic alterations and associating it with clinical outcome. In neuroblastoma, genomic alterations have been investigated by cytogenetic, and molecular methods including spectral karyotyping and metaphase comparative genomic hybridization (M-CGH) [2] [3] [4] [5] [6]. Here, we focus on DNA copy number alterations in NB detected by the recently developed cDNA array-based comparative genomic hybridization (A-CGH). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastoma (NB) is one of the most common pediatric solid tumors and displays a broad variety of genomic alterations. Array-based comparative genomic hybridization (A-CGH) is a novel technology enabling the high-resolution detection of DNA copy number aberrations. In this article, we outline features of this new technology and approaches of data analysis. We focus on stage specific DNA copy number variations in neuroblastoma detected by cDNA array-based comparative genomic hybridization (A-CGH). We also discuss hypothetic evolutionary models of neuroblastoma progression that can be derived from A-CGH data.
    Cancer Letters 11/2005; 228(1-2):71-81. DOI:10.1016/j.canlet.2004.12.056 · 5.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Molecular studies of advanced-stage neuroblastoma (NBL) have revealed a marked genetic heterogeneity. In addition to MYCN amplification and chromosome 1 short-arm deletions/translocations detected by conventional cytogenetics, application of fluorescence in situ hybridization has disclosed a high prevalence of 17q gain, whereas allelotyping and comparative genomic hybridization techniques also have revealed loss of 11q and of other chromosomal material. Using the recently developed technique of spectral karyotyping (SKY), we sought to refine the cytogenetic information, identify hidden recurrent structural chromosomal abnormalities, and compare them to the molecular findings. Thirteen samples of metaphase spreads from 11 patients with advanced-stage NBL were analyzed by SKY. Most of them were found to have complex karyotypes (more than three changes per metaphase) and complex unbalanced rearrangements. Recurrent aberrations leading to 17q gain, deletion of 1p, MYCN amplification, and loss of 11q appeared in 7, 4, 4, and 5 patients, respectively, in simple and complex karyotypes. Chromosome 3 changes and gain of 1q and 7q appeared in 6, 5, and 4 patients, respectively, in complex karyotypes only, reflecting later changes. A strikingly high prevalence of the unbalanced translocation der(11)t(11;17), leading to concomitant 11q loss and 17q gain in 4 patients, delineated a distinct cytogenetic group, none having 1p deletion and/or MYCN amplification. der(11)t(11;17) was associated with complex karyotypes with changes in chromosomes 3 and 7q. The 17q translocations with partners other than 11q were associated with 1p deletion and/or MYCN amplification. The distinct cytogenetic subgroups identified by SKY confirm and extend the recent molecular observations, and suggest that different genes may interact in the der(11)t(11;17) pathway of NBL development and progression.
    Genes Chromosomes and Cancer 07/2002; 34(3):313-24. DOI:10.1002/gcc.10082 · 3.84 Impact Factor
Show more